A 5:2 Intermittent Fasting Meal Replacement Diet and Glycemic Control for Adults With Diabetes

Key Points Question What is the effect of a 16-week intermittent fasting plan consisting of 2 nonconsecutive fasting days and 5 days of habitual intake per week and meal replacement diet (5:2 MR) on the changes in hemoglobin A1c level in Chinese adults with early type 2 diabetes? Findings In this randomized clinical trial of 405 adults, the 5:2 MR approach achieved better glycemic control at 16 weeks compared with metformin and empagliflozin. Meaning The 5:2 MR approach may serve as an effective initial lifestyle intervention instead of antidiabetic drugs for patients with type 2 diabetes.

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eMethods. Multiple Imputation
In this study, multiple imputation was employed under the assumption of "missing at random" (MAR).This means that the probability of data being missing is unrelated to the missing values themselves but is only related to the observed data.For the imputation of continuous variables, we utilized a linear regression model.In this approach, each variable with missing data was modeled as a function of the other variables in the dataset.The linear regression model was used to estimate the relationships between the variables, and these relationships were then used to predict the missing values.Specifically, the missing value for a particular variable was estimated as a linear combination of the observed values of the other variables, with the coefficients determined by the regression model.The process of multiple imputation involves creating several imputed datasets, each with slightly different imputed values.This is done to account for the uncertainty in the imputation process.The analysis is then performed on each of these datasets separately, and the results are combined to produce a single set of estimates that reflect the variability due to missing data.eTable 2. The Contents of Dietary and Exercise Guidance, and General Diabetes Education for All Participants

Item
Contents 1

General Diabetes Education
Diabetes overview, chronic complications and comorbidities of diabetes, acute complications of diabetes, psychological stress and coping in diabetes patients.

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Calculation of Ideal Weight Ideal weight (kg) =Height (cm) -105.Within ± 10% of this value, it is within the normal range.

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Based on ideal weight and participation in physical labor, the total daily calorie intake from food can be calculated.

II. Reasonable arrangement of meals
Diabetes patients should have at least three meals a day, so that staple food and protein are evenly distributed in the three meals, and they should be rationed regularly, generally according to 1/5, 2/5 or 1/3.For those who are prone to hypoglycemia, a small portion of staple food can be evenly distributed in the main meal as an additional meal between the two main meals.In addition to the main course, protein foods such as milk, eggs, and dried tofu can be added to the bedtime meal.

IV. Scientific selection of fruits
When the fasting blood glucose is controlled below 7.0mmol/L (126mg/dl), the postprandial blood glucose is less than 10mmol/L (180mg/dl), the glycated hemoglobin is less than 7.5%, and there is no significant fluctuation in blood glucose, fruits can be chosen.It is best to eat between two meals.Those who are not satisfied with disease control should not eat it temporarily.They can eat a small amount of raw cucumbers and tomatoes.

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Carbohydrates Sweet potatoes, potatoes, yams, taro, lotus roots and other root vegetables have a high starch content and cannot be eaten casually.They need to be exchanged with grain.Strictly limit the intake of white sugar, brown sugar, honey, jam, chocolate, various sweets, sugary drinks, ice cream and various sweet Dim sum.

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Fat and cholesterol diabetes patients should eat less fried food.Nuts are high in fat content and should be consumed less.The daily intake of cholesterol should be less than 300 milligrams.

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Vitamin and mineral diabetes patients can eat more fresh vegetables, and try to eat raw as much as possible to ensure the full absorption of vitamin C and other nutrients.The intake of salt should be limited to 6 grams per day.

Exercise Guidance I. Preparation before exercise
Before starting any exercise plan, patients undergoing a comprehensive physical examination should thoroughly screen for any potential complications, exclude potential diseases or injuries, and exclude risk factors to ensure exercise safety.
Make exercise plans and discuss with doctors or full-time diabetes educators whether their physical conditions are suitable for exercise, and determine the exercise mode and amount.If blood glucose is less than 5.6 mmol/L, additional carbohydrates should be consumed before exercising.

II. Exercise style, intensity, time, and frequency
The exercise intensity selected by diabetes patients should be 60~70% of the maximum exercise intensity.The intensity of exercise can also be controlled based on one's feelings, that is, the whole body is hot and sweating, but not sweating profusely.Patients with diabetes can choose moderate and low-intensity aerobic exercise.Exercise should be carried out about 1-2 hours after the start of a meal because blood glucose is high at this time and low blood glucose is less likely to occur during exercise.The duration of each exercise is approximately 30-60 minutes.The frequency of exercise diabetes patients should adhere to at least 3 to 4 times of moderate and low-intensity exercise every week.to replace all three meals with Kang zhijun™ A. The dietary plan for these two days is as follows as example: one egg for breakfast + Kang zhijun™ A, 100g of low-sugar fruit (such as cucumber, tomato and orange) for lunch + Kang zhijun™ A, and 200-400g of green leafy vegetables (such as spinach and cabbage) for dinner + Kang zhijun™ A. The specified total daily energy intake is 500 kcal for females and 600 kcal for males per day.For the remaining 5 days of the week, breakfast and lunch should be regular meals (less intake of oil and sugar is recommended), and dinner will be replaced with Kang zhijun™ B.

eFigure 1 .
Study design.Participants were randomly assigned to the metformin, empagliflozin, or 5:2 MR groups for a 16-week treatment.After the 16-week treatment, the participants in all three groups underwent an additional 8-week follow-up without any intervention, i.e., the final visit was conducted at week 24.eFigure 2. The 5:2 MR approach.Participant are required to choose 2 nonconsecutive days within a week (such as Monday and Thursday, or Tuesday and Friday) Multiple Imputation eTable 1. Study Centers, Location, Ethics Committee Approvals eTable 2. The Contents of Dietary and Exercise Guidance, and General Diabetes Education for All Participants eTable 3. Nutrition Facts of Kang Zhijun™ eTable 4. Changes in Primary and Secondary Outcomes From Baseline to Week 16 (Intention-to-Treat Analysis) eTable 5. Unadjusted Analyses of Outcomes From Baseline to Week 16 in the Three Groups eTable 6.Primary and Secondary Outcomes From Baseline to Week 16 in Three Groups (Completers Analysis) eTable 7. Primary and Secondary Outcomes From Baseline to Week 24 in Three Groups (Completers Analysis) eFigure 1. Study Design eFigure 2. The 5:2 MR Approach eFigure 3. Changes in Body Weight eFigure 4. Post-Hoc Subgroup Analysis of Weight Loss at Week 16 by Intention-to-Treat Analysis eReference. eMethods.
For the remaining five days of the week, patients followed their regular diet for breakfast and lunch, and used one serving of Kang zhijun™ B (20g dissolved in 200ml of water) to replace dinner.Each serving of meal powder B provided 88 kcal with 12.7g of carbohydrates, 3.9g of protein, and 2.3g of fat.Changes in Primary and Secondary Outcomes from Baseline to Week 16 (Intention-to-Treat Analysis) a Unadjusted a Analyses of Outcomes From Baseline to Week 16 in the Three Groups Primary and Secondary Outcomes from Baseline to Week 16 in Three Groups (Completers Analysis) IngredientsMedium-chain triglycerides, extra virgin olive oil, sea buckthorn oil, DHA algal oil, maltodextrin, fructo-oligosaccharides, whole milk powder, soy protein powder, inulin, xylitol, sweet orange powder, cheese powder, calcium (calcium carbonate), iron (ferric pyrophosphate), zinc (zinc oxide), vitamin A, vitamin D, vitamin E, vitamin b Abbreviations: HbA1c, glycated hemoglobin; HDL, high-density lipoprotein cholesterol; HOMA-IR, homeostasis model assessment of insulin resistance; LDL, lowdensity lipoprotein cholesterol.Data are adjusted LSM (SE).aThefollowingcovariates were used for adjustment in this analysis: sex, age, height, weight, family history of diabetes and hypertension, physical activity, smoking, alcohol consumption, and baseline.eTable5.Abbreviations: HbA1c, glycated hemoglobin; HDL, high-density lipoprotein cholesterol; HOMA-IR, homeostasis model assessment of insulin resistance; LDL, lowdensity lipoprotein cholesterol.Data are mean (SD).aAll patients in the full analysis set are included in the treatment comparisons, without adjustment for the following baseline characteristics (sex, age, height, weight, family history of diabetes and hypertension, physical activity, smoking, alcohol consumption, and baseline HbA1c).eTable 6.